Just to clarify a few things....
Have you just "run" Game Jackal? No profiles loaded or anything like that, just run the program, and it should come up on the screen with the options to create a profile and such.
Have you tried any other games with Game Jackal, preferably games without SecureROM protection? Do you have multiple CD/DVD drives? Are they SATA drives, or the older EIDE CD/DVD drives?
Windows Vista and Game Jackal do not always cooperate when it comes to certain copy protection systems, and it even seems to be a problem only for certain games on some systems, but not others. For myself, I can get just about everything to work with Game Jackal and Vista Home Premium, but Neverwinter Nights 2 just won't work for me as an example...yet the same game works on another system I have but with Windows XP.
These are the reasons why you need to be very specific about what game(s) you have problems with, as well as settings and such. Slysoft is working very hard to track down the source of problems, but with ambiguous information from people, it is impossible(not just hard) for them to isolate the source(s) of problems. There is a big difference between "Please insert the correct CD", and the application crashing, or the ever popular blue screen of death(having Mask of the Betrayer in the drive will cause this on my Vista machine).
Please note that if NOTHING works for you, that may indicate that Game Jackal itself was not installed correctly(some weird glitch), you have a CD/DVD in the drive, you have a SATA CD/DVD drive in your system, or you have some other program installed that is causing a conflict with your CD/DVD drive. In most cases, programs like Nero also install services into Windows which continue to run, even if you have turned off virtual drives.
With Vista being so new(yes, I know we are getting close to it being out for a year for corporate customers), but there are still a number of issues that have yet to be resolved. Just having a program installed may be enough to cause unknown issues in Vista is what I am trying to say.